The overall prime aim of this proposed study is to develop a complete functional model for the mechanisms whereby various components of the brainstem respiratory control system integrate afferent information from the peripheral and central chemoreceptors in order to produce appropriate ventilatory alterations. In this context, previous results from this laboratory have implied that a fundamental difference may exist between the brainstem mechanisms responsible for peripheral chemoreceptor integration as compared to those responsible for central chemoreceptor integration. This difference in integrative mechanisms might reflect a difference in the prime anatomical site of termination of peripheral and central chemoreceptor afferents within the brainstem and/or represent a difference in the distribution of chemoreceptor afferents within a specific brainstem site. These hypotheses will be primarily evaluated by the extracellular monitoring of single respiratory units at one or more simultaneous sites within the brainstem prior to and following physiological and pharmacological stimulation of the peripheral and central chemoreceptors. Similar monitoring of respiratory units will be performed concomitant with the functional blockade of the peripheral or central chemoreceptors. The differential integration of chemoreceptor afferent stimuli will also be evaluated by examination of the pattern of efferent phrenic unit recruitment in response to hypercapnic or hypoxic stimuli. The relative contribution of peripheral chemoreceptor mechanisms and the interaction of peripheral and central chemoreceptor afferent stimuli within the brainstem in defining ventilatory responses to hypercapnic-hypoxic stimuli will also be evaluated.